Palladium-catalyzed intramolecular carbopalladation/cyclization cascade: access to polycyclic N-fused heterocycles

An efficient palladium-catalyzed intramolecular carbopalladation/cyclization cascade toward tetra- and pentacyclic N-fused heterocycles has been developed. This transformation proceeds via the palladium-catalyzed coupling of aryl halides with internal propargylic esters or ethers followed by the 5-endo-dig cyclization leading to polycyclic pyrroloheterocycles in moderate to excellent yields.     

Intramolecular cyanoboration of alkynes via activation of boron-cyanide bonds by transition metal catalysts

Cyano(dialkylamino)boryl ethers of homopropargylic alcohols undergo intramolecular addition of a B-CN bond across their carbon-carbon triple bonds (cyanoboration) in the presence of palladium and nickel catalysts, furnishing five-membered cyclic boryl ethers regioselectively in good yields via 5-exo cyclization. The products were transformed into highly substituted α,β-unsaturated nitriles via Suzuki-Miyaura coupling to aryl iodides, rhodium-catalyzed conjugative addition to methyl vinyl ketone, and rhodium-catalyzed protodeborylation.     

Potassium tert-butoxide promoted intramolecular arylation via a radical pathway

Potassium tert-butoxide mediated intramolecular cyclization of aryl ethers, amines, and amides was efficiently performed under microwave irradiation to provide the corresponding products in high regioisomeric ratios. The reaction proceeds via single-electron transfer to initiate the formation of an aryl radical, followed by a kinetically favored 5-exo-trig and subsequent ring expansion.     

The selective reaction of aryl halides with KOH: synthesis of phenols, aromatic ethers, and benzofurans

The direct and selective synthesis of phenols from aryl/heteroaryl halides and KOH has been achieved through the use of highly active monophosphine-based catalysts derived from Pd(2)dba(3) and ligands L1 or L2 and the biphasic solvent system 1,4-dioxane/H(2)O. We have also demonstrated a one-pot method of phenol formation/alkylation for the preparation of alkyl aryl ethers from aryl halides. In many instances, this protocol overcomes limitations in existing Pd-catalyzed coupling reactions of aliphatic alcohols with aryl halides. Finally, we demonstrate that substituted benzofurans can be prepared efficiently via a Pd-catalyzed phenol formation/cyclization protocol starting from 2-chloroaryl alkynes.     

Oxidative Prins and Prins/Friedel-Crafts cyclizations for the stereoselective synthesis of dioxabicycles and hexahydro-1H-benzo[f]isochromenes via the benzylic C-H activation

1-Benzyl ethers of (E)- and (Z)-hex-3-en-1,6-diols and hept-3-en-1,7-diols undergo a smooth oxidative cyclization with DDQ in the presence of In(OTf)(3) through a sequential C-H bond activation and an intramolecular Prins cyclization to afford the corresponding trans- and cis-fused hexahydro-2H-furo[3,2-c]pyrans and octahydropyrano[4,3-b]pyrans respectively in good yields with an excellent stereoselectivity. Aryl tethered homoallylbenzyl ethers such as benzyl ethers of (E)- and (Z)-6-arylhex-3-enyl alcohols undergo a tandem Prins/Friedel-Crafts cyclization in the presence of stoichiometric amounts of DDQ and SnCl(4)via the benzylic C-H bond activation to furnish the corresponding trans- and cis-fused hexahydro-1H-benzo[f]isochromenes in good yields with complete stereoselectivity.     

Room Temperature Copper(II)-Catalyzed Oxidative Cyclization of Enamides to 2,5-Disubstituted Oxazoles via Vinylic C-H Functionalization

A copper(II)-catalyzed oxidative cyclization of enamides to oxazoles via vinylic C-H bond functionalization at room temperature is described. Various 2,5-disubstituted oxazoles bearing aryl, vinyl, alkyl, and heteroaryl substituents could be synthesized in moderate to high yields. This reaction protocol is complementary to our previously reported iodine-mediated cyclization of enamides to afford 2,4,5-trisubstituted oxazoles.     

Palladium-catalyzed, stereoselective, cyclizative alkenylboration of carbon-carbon double bonds through activation of a boron-chlorine bond

Palladium-catalyzed alkenylboration of carbon-carbon double bonds has been achieved using the reaction of chloro(diisopropylamino)boryl ethers of homoallylic alcohols with alkenylzirconium reagents. The reaction may proceed through an initial oxidative addition of the B-Cl bond, intramolecular insertion of the C═C bond into the B-Pd bond, transmetalation from the alkenylzirconium reagent, and reductive elimination of the products. The cyclization proceeds with high diastereoselectivity for the formation of cis-3,5- or trans-3,4-disubstituted-1,2-oxaborolane products. Cross-coupling of the resultant products with aryl iodides proceeds with retention of configuration at the boron-bound secondary carbon atom.     

Tandem Rh(III)-catalyzed oxidative acylation of secondary benzamides with aldehydes and intramolecular cyclization: the direct synthesis of 3-hydroxyisoindolin-1-ones

The rhodium-catalyzed oxidative acylation between secondary benzamides and aryl aldehydes via sp(2) C-H bond activation followed by an intramolecular cyclization is described. This method results in the direct and efficient synthesis of 3-hydroxyisoindolin-1-one building blocks.     

Rhodium(III)-catalyzed cyclization-olefination of N-acetoxyl ketoimine-alkynes

N-Acetoxyl ketoimine-alkynes undergo Rh(III)-catalyzed oxidative olefination to afford (2-acetoxymethyl)isoquinolines bearing an ortho-olefinated aryl group via a sequence that involves (1) Rh(III)-catalyzed alkyne cyclization with intramolecular 1,3-acetoxyl migration and (2) isoquinoline-directed ortho C-H olefination.     

A Garratt-Braverman route to aryl naphthalene lignans

A series of aryl naphthalene lignans were prepared in good yields starting from substituted bis-propargyl ethers. The method involved a base-mediated Garratt-Braverman cyclization followed by benzylic oxidation to the lactone. The chemoselectivity in the GB cyclization and the regioselectivity in the benzylic oxidation could be achieved by controlling the electronic nature of the aryl-substituents as well as by changing the substitution pattern of the two aryl rings.     

Oxidative conversion of silyl enol ethers to α,β-unsaturated ketones employing oxoammonium salts

The oxidative conversion of silyl enol ethers to α,β-unsaturated ketones using a less-hindered class of oxoammonium salts (AZADO(+)BF(4)(-)) is described. The reaction proceeds via the ene-like addition of oxoammonium salts to silyl enol ethers.     

Bis(triarylmethylium)-mediated diaryl ether synthesis: oxidative arylation of phenols with N,N-dialkyl-4-phenylthioanilines

Various aryl 4-dialkylaminophenyl ethers were readily synthesized without heating in good yield from phenols and N,N-dialkyl-4-phenylthioanilines. This oxidative arylation of phenols was successfully promoted by a bis(diphenylmethylium)naphthalenediyl dication via ipso-substitution of the phenylthio group in the anilines through a radical process.     

One-pot synthesis of aryl fluorides by [3+3] cyclization of 1,3-bis(silyl enol ethers) with 2-fluoro-3-silyloxy-2-en-1-ones

Functionalized aryl fluorides were regioselectively prepared by [3+3] cyclization of 1,3-bis(silyl enol ethers) with 2-fluoro-3-silyloxy-2-en-1-ones.     

Rearrangement of Aryl Geranyl Ethers

This article describes the thermal rearrangement reactions of aryl geranyl ethers. These reactions depend on the structure of the aryl moiety of the substrate and the reaction conditions used. The naphthyl ethers underwent a [1,3]-alkyl shift, followed by acid-catalyzed intramolecular cyclization. The microwave-assisted rearrangement of isoquinolinyl ether showed a pattern of an abnormal Claisen rearrangement. The multi step rearrangement of the quinolyl ether afforded a spiro compound. These new reactions were used to synthesize novel heterocyclic compounds.     

A new five-membered ring forming process based on palladium(0)-catalyzed arylative cyclization of allenyl enones

A palladium(0)/monophosphine catalyst promotes a novel arylative cyclization reaction of C1-, C2-, and C3-tethered allenyl enones with arylboronic acids to produce five-membered ring containing products. The regioselectivity of the process, associated with aryl group introduction into the allene moiety, depends on the length of the tether. This finding suggests that the cyclization reaction does not proceed through a carbopalladation pathway but rather via a route involving palladacycle-forming or "anti-Wacker"-type oxidative addition to the Pd(0) catalyst.     

Palladium-catalyzed cycloaddition of alkynyl aryl ethers with internal alkynes via selective ortho C-H activation

Alkynyl aryl ethers react with internal alkynes through selective ortho C-H activation by a palladium(0) catalyst to give substituted 2-methylidene-2H-chromenes. The alkynoxy group acts as a directing group to promote ortho C-H functionalization. Deuterium-labeling experiments indicated that the arylpalladium hydride complex is a key intermediate via oxidative addition. Various functional groups tolerate the present transformation to give the corresponding products.     

Microwave-accelerated spiro-cyclizations of o-halobenzyl cyclohexenyl ethers by palladium(0) catalysis

A number of new spiro[cyclohexane-1,1'-isobenzofuran]-based compounds was synthesized by palladium(0)-catalyzed 5-exo cyclization of a series of cyclohexenyl o-halobenzyl ethers. Controlled microwave heating was found to promote both product yield and reaction rate without compromising the selectivity. Heck cyclization of aryl iodide 6, 2-(2-iodobenzyloxy)cyclohex-2-enyl acetate, proceeded selectively without involvement of the allylic acetate functionality.     

Synthesis of biaryls by intramolecular radical aryl migration from silicon to carbon

A new method for the preparation of biaryls via intramolecular 1,5 aryl migration reaction from silicon in silyl ethers to aryl radicals is presented. Various readily available diphenylsilyl ethers can be used as substrates in this reaction. Functionalized aryl groups can also be transferred. The analogous 1,4 aryl migration reaction is less efficient.     

碱性介质中邻硝基芳香醚的醚键稳定性研究

设计合成了一系列的邻硝基芳香醚,对碱性介质中芳醚键的稳定性进行了研究。选用对硝基甲苯为内标,用高效液相色谱仪对邻硝基芳香醚的醚键断裂程度进行了分析,并用内标法计算出它们的转化率。结果表明,由于-NO2的存在,邻硝基芳香醚在碱性溶液中易发生亲核取代反应,使醚键断裂,从而使这类化合物出现不稳定性。发现邻硝基苯氧丙酸亲核取代的异常情况,推测可能是分子内邻基参与的亲核取代反应。     

Synthesis of Benzofuran Derivatives through Cascade Radical Cyclization/Intermolecular Coupling of 2‐Azaallyls

Benzofurans are among the most popular structural units in bioactive natural products, however, the synthesis of such structures by radical cyclization cascade reactions is rare. Herein, we report a mild and broadly applicable method for the construction of complex benzofurylethylamine derivatives through a unique radical cyclization cascade mechanism. Single‐electron transfer (SET) from 2‐azaallyl anions to 2‐iodo aryl allenyl ethers initiates a radical cyclization that is followed by intermolecular radical–radical coupling. This expedient approach enables the synthesis of a range of polycyclic benzofurans that would otherwise be difficult to prepare.